PROJECT SUMMARY Lung cancer is the leading cause of cancer death and cardiovascular disease is the overall leading cause of death among American Indians (AI). A major risk factor contributing to this premature mortality is the fact that AI have the highest smoking rates of all major ethnic groups in the US, at 31.8%, nearly double that of both African Americans and Whites. Despite these high rates of smoking and tobacco-related illness, few researchers have addressed this issue, in part because tobacco is a sacred plant to many AI and cannot be treated completely negatively, as most smoking cessation programs do. Researchers at the University of Kansas Medical Center (KUMC) and Johnson County Community College (JCCC) have been working with AI communities using community-based participatory research (CBPR) to address recreational tobacco since 2003. Together we have developed a successful culturally tailored cessation program, All Nations Breath of Life (ANBL), that respects tobacco as a sacred plant and promotes honoring it rather than abusing it recreationally. Our in-person, group-based program had an intent-to-treat quit rate of 27.9% versus 17.4% in a current best practices comparison arm at end of treatment (12 weeks) in a reservation-based efficacy trial (N=463). Cessation rate was 20% vs. 12% at 6 months (p=0.02). In a large urban implementation feasibility pilot (N=312 across sites in five states), our quit rate was 22% at 6-months (p<0.002 compared to the highest previously reported quit rates for an urban AI population); our retention rate was 71%. Because ANBL has been proven efficacious in reservation populations and shows promise in urban populations and because of the significance of the tobacco abuse problem in both reservation and urban AI communities, we believe it prudent to move towards expeditious implementation and dissemination of ANBL. Therefore, we propose continued efficacy testing through an effectiveness-implementation type 2 hybrid design. This design allows for efficacy testing with simultaneous implementation testing to move the program towards large-scale dissemination at the conclusion of the study. We will address the following specific aims: (1) To assess 7-day point prevalence expired CO validated quit rates at 6 months (24 weeks) at each community site among participating individuals following randomization and implementation of ANBL in two urban and two reservation communities (N=576), using a waitlist control design. We hypothesize that quit rates will be 21% in the ANBL arm and 9% in the waitlist control arm of individuals at each site; (2) To identify programmatic and organizational factors that enhance implementation of ANBL and contribute to program success or failure guided by RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and Consolidated Framework for Implementation Research (CFIR) approaches; and (3) To compare different resources and costs used in each grantee site for delivery of ANBL.